fetalcirculation and physiology presentation

Fetal circulation and physiology

1. FETAL CIRCULATION AND PLACENTAL TRANSFER OF ANESTHETIC DRUGS PRESENTER: Dr. RUCHI MODERATOR: Dr.GANESH / Dr.HARDIKA

2. The Fetal Circulation

3. 3 unique FETAL CVS structures : THREE SHUNTS

4. COURSE OF FETAL CIRCULATION: 1.Placenta: Has the lowest vascular resistance in the fetus. Receives the largest amount of combined ( Rt + Lt) Ventricular Output (55%) 2. Superior Vena Cava: Drains the upper part of the body,including the brain (15% of combined ventricular output). Most of SVC blood goes to the Right Ventricle.

5. 3. Inferior Vena Cava: Drains lower part of body and placenta (70% of combined ventricular output) Part of IVC blood with high O2 goes into LA via Foramen Ovale . Remaining IVC blood enter RV and Pulmonary artery. Since blood is oxygenated in the placenta, Oxygen saturation in IVC (PO2 = 26-28%) is higher than that in SVC (12-14%).

6. Most of SVC blood (less oxygenated blood) goes into RV. Most of IVC blood (high O2 concentration) is directed by the Crista Dividens to the LA through Foramen ovale . Rest of IVC blood enters RV & pulmonary artery. Less oxygenated blood in Pulmonary artery flows through Ductus Arteriosus to descending aorta and then to placenta for oxygenation.

7. The Result is: Brain and coronary circulation receive blood with higher concentration (PO2 = 28 mm Hg) than the lower part of the body (PO2 = 24 mm Hg)

8. FETAL CIRCULATION: The pathway: Placenta  Oxygenated blood  U mbilical vein Hepatic circulation Bypasses liver & joins IVC via ductus venosus Partially mixes with poorly oxygenated IVC blood derived from lower part of fetal body

9. From the right ventricle  P ulmonary artery. Because the pulmonary arterial circulation is vasoconstricted , only about 10% of right ventricular outflow enters the lungs. The rest 90% blood (which has a PO 2 of ≈18–22 mm Hg) bypasses the lungs and flows through the ductus arteriosus into the descending aorta to perfuse the lower part of the fetal body. It then returns to the placenta via the two umbilical arteries.

10. LA  LV  Aorta  Ductus arteriosus Foramen ovale RV SVC  upper body IVC 50% through 50% to ductus venosus Portal circulation Umbilical Vein Oxy.blood PLACENTA Pulm artery  Lungs

11. Aorta Deoxygenated blood Descending aorta Abdominal aorta Common iliac artery Umbilical arteries PLACENTA Oxygenation Umbilical Vein

12. FETAL CIRCULATION: The total fetal cardiac output—the combined output of both the left and right ventricles—is ≈ 450 mL /kg/min. Descending aortic blood flow : -65%  returns to placenta; -Remaining 35%  perfuses the fetal organs & tissues. Right ventricular output is about 1.3 times the left ventricular flow. Thus, during fetal life the right ventricle -is pumping against systemic blood pressure -is performing greater volume of work than LV.

13. The Transitional Circulation

14. TRANSITIONAL CIRCULATION: At birth Mechanical expansion of lungs Increase in arterial PO 2 Rapid DECREASE in pulmonary vascular resistance Removal of the low-resistance placental circulation INCREASE in systemic vascular resistance.

15. TRANSITIONAL CIRCULATION: Right ventricle output now flows entirely into the pulmonary circulation. Pulmonary vascular resistance becomes lower than systemic vascular resistance, Shunt through ductus arteriosus reverses & becomes left to right.

16. TRANSITIONAL CIRCULATION: High arterial PO 2 (In several days) Constriction of ductus arteriosus It closes, becoming the ligamentum arteriosum .

17. TRANSITIONAL CIRCULATION: Increased volume of pulmonary blood flow returning to left atrium Increases left atrial volume and pressure Closure of foramen ovale (functionally) (Although the foramen may remain probe patent) Becomes Fossa Ovalis

18. Removal of the placenta from the circulation Also results in closure of the ductus venosus . The left ventricle is now coupled to the high-resistance systemic circulation  its wall thickness and mass begin to increase. In contrast, the right ventricle is now coupled to the low-resistance pulmonary circulation  its wall thickness and mass decrease slightly.

19. The left ventricle in the fetus pumped blood only to the upper part of the body and brain After birth, LV must deliver the entire systemic cardiac output (≈350 mL /kg/min). (almost 200% increase in output) This marked increase in left ventricular performance is achieved through a combination of hormonal and metabolic signals, including an INCREASE IN : -The level of circulating catecholamines and -The myocardial receptors (β-adrenergic) (through which catecholamines have their effect)

20. Patency of these fetal pathways may either : Provide a lifesaving pathway for blood to bypass a congenital defect ( eg : -Patent ductus in Pulmonary atresia or COA. -Foramen ovale in Transposition of the great vessels) or Present an additional stress to the circulation ( eg : -Patent ductus arteriosus in a premature infant, - Rt Lt shunt in infants with pulmonary hypertension) Therapeutic agents may either : Maintain fetal pathways open - PGE 1 Promote their closure - Indomethacin

21. Fetal vs. Infant Circulation Fetal Low pressure system Right to left shunting Lungs non-functional Increased pulmonary resistance Decreased systemic resistance Infant High pressure system Left to right blood flow Lungs functional Decreased pulmonary resistance Increased systemic resistance

22. CLOSURE of: Foramen ovale : Functional Closure: 3rd month of life. Anatomical closure of septum primum & septum secundum by 1 year of age. Ductus arteriosus : Functional Closure: By 10–15 hr in a normal neonate. Anatomic closure: May take several weeks.

23. Summary

24. DRUG TRANSFER Total drug transferred to fetus = Maternal conc X F: M ratio of drug F:M Ratio = umbilical Vein Vs maternal venous concentration MORE IS THE F:M RATIO;; MORE IS THE TRANSFER OF THE DRUG

25. FACTORS AFFECTING PLACENTAL DRUG TRANSFER 1. SUBSTANCE PROPERTIES 2. MATERNAL PROPERTIES 3. PLACENTAL PROPERTIES

26. SUBSTANCE PROPERTIES Molecular weight : lower the mol wt, more is the transfer. Lipid solubility: lipophilic substances diffuse easily. Ionization: Nonionized molecules diffuse easily.

27. If the pH of maternal blood changes (e.g. in labour ) then changes in the degree of drug ionization and transfer can occur. Ph of blood: Lower Ph favours ionization. Protein binding:Drugs which are protein-bound do not diffuse across the placenta; only the free, unbound portion of a drug is free to cross the cell membranes. Protein binding is altered in a range of pathological conditions. For example, low serum albumin in pre-eclampsia will result in a higher proportion of unbound drug and will therefore promote drug transfer across the placenta.

28. Three types of drug transfer across the placenta are recognized: ( i ) Complete transfer (type 1 drugs): for example, thiopental Drugs exhibiting this type of transfer will rapidly cross the placenta with pharmacologically significant concentrations equilibrating in maternal and fetal blood. (ii) Exceeding transfer (type 2 drugs): for example, ketamine These drugs cross the placenta to reach greater concentrations in fetal compared with maternal blood. (iii) Incomplete transfer (type 3 drugs): for example, succinylcholine These drugs are unable to cross the placenta completely, resulting in higher concentrations in maternal compared with fetal blood.

29. MATERNAL PROPERTIES Drug concentration in the maternal blood. Uterine blood flow. UBF =(uterine arterial pressure – uterine venous pressure) / uterine vascular resistance Normal value=500-600 ml/min at term Concentration gradient on either side of placental membranes.

30. PLACENTAL PROPERTIES Lipid membrane of placenta enhances transfer. Total surface area of the placental membrane. Functional integrity and thickness of the placental barrier.

31. PLACENTAL TRANSFER OF ANAESTHETIC DRUGS Induction agents:Thiopental rapidly crosses the placenta and is quickly cleared by the neonate after delivery. Propofol is also very lipid soluble and able to cross the placenta easily. It has been associated with transient depression of Apgar scores and neurobehavioural effects in the neonate.

32. Inhalation agents: Volatile anaesthetic agents readily cross the placenta as they are highly lipid soluble and have low molecular weights. A prolonged dose-delivery interval results in greater transfer and therefore a greater sedative effect on the neonate. Nitrous oxide also crosses the placenta rapidly. Diffusion hypoxia can occur in neonates exposed to nitrous oxide immediately before delivery and therefore supplemental oxygen may be required.

33. Neuromuscular blocking agents are large, poorly lipid soluble, and highly ionized molecules. They cross the placenta very slowly and pose no significant clinical problems to the neonate. Opioids : Meperidine is 50% plasma protein-bound and crosses the placenta readily. Maximal uptake by the fetal tissues occurs 2–3 h after a maternal i.m . dose, and this is the time when neonatal respiratory depression is most likely to occur.

34. Morphine is less lipid soluble but because of its poor protein binding, it readily crosses the placenta. Fentanyl is very lipid soluble and crosses the placenta rapidly. Remifentanil crosses the placenta but is rapidly metabolized by the fetus and its use for labour analgesia has not been associated with adverse neonatal effects. Local anaesthetics : Bupivacaine and ropivacaine are highly lipid soluble but have a high degree of protein binding. Lidocaine is less lipid soluble than bupivacaine but has a lower degree of protein binding, so it will also cross the placenta. Local anaesthetics can accumulate in the fetus due to ‘ion trapping’if the fetus becomes acidotic . Ion trapping occurs when the decreased pH in the fetus produces an increased proportion of ionized drug which is then unable to cross the placenta.

35. Glycopyrrolate -quaternary ammonium compound fully ionized poorly transferred across placenta. Atropine- lipid-soluble tertiary amine complete placental transfer. Neostigmine - quaternary ammonium compound but small molecule able to cross the placenta more rapidly than glycopyrrolate .

36. In a few cases where neostigmine has been used with glycopyrrolate to reverse non-depolarizing neuromuscular block in pregnancy, profound fetal bradycardia has been reported. Consequently, for general anaesthesia in pregnancy where the baby is to remain in utero , it may be advisable to use neostigmine with atropine rather than with glycopyrrolate . Benzodiazepines are highly lipid soluble and unionized and therefore exhibit rapid and complete diffusion across the placenta.

37. Drugs crossing placenta Anticholinergics Atropine Scopolamine Antihypertensive agents Beta-adrenergic receptor antagonists Nitroprusside Nitroglycerine Benzodiazepines Diazepam Midazolam Induction Agents Propofol Thiopentone

38. Inhalational anaesthetic Agents Halothane Isoflurane Nitrous oxide Local Anaesthetics Opioids Vasopressors Ephedrine

39. Drugs that Do Not Cross the Placenta Anticholinergic Glycopyrrolate Anticoagulants Heparin Muscle Relaxants Depolarizing – succinylcholine NDMRs

40. FDA Classification of anaesthetic drugs The United States Food and Drug Administration has proposed a classification for drugs used in pregnancy to suggest the risk of affecting embryo-fetal development. . Category A - Controlled studies showed absence of risk . Category B - Without evidences of human risk . Category C - The risk cannot be ruled out . Category D - Positive evidence of risk Category X - Contraindicated in pregnancy The only drug specifically approved by the FDA for use during pregnancy is ritodrine(adrenergic beta agonist) administered to pregnant women in order to halt preterm labor

41. FDA Classification of anaesthetic drugs DRUGS Cat. B Cat. C Cat. D Cat. X ANALGESIC Diclofenac Opioids GENERAL ANAESTHETIC Enflurane , Sevoflurane , Propofol Halothane,Isoflurane,Thiopentone , Ketamine,Etomidate Nitrous Oxide LOCAL ANAESTHETIC Ropivacaine , Lidocaine Bupivacaine ANTICHOLINERGIC Atropine, Glycopyrrolate ANTIEMETIC Ondansetron,Metoclopromide BENZODIAZEPINES Midazolam B-BLOCKERS Esmolol,Labetolol , Propranolol

42. Thank you!